免疫耐受期慢性乙型肝炎病毒感染者的临床病理分析

Clinicopathological analysis in patients with chronic hepatitis B virus infection in immune tolerant phase

目的分析免疫耐受期(IT)慢性乙型肝炎病毒(HBV)感染者的肝组织病理特征及临床意义。方法纳入2015年1月至2019年12月在中国科学院大学宁波华美医院就诊的273例接受肝脏穿刺活检术的IT期慢性HBV感染患者的临床资料,分析其肝脏病理学改变及与临床特征的相关性。结果肝组织学≥炎症分级2级(G2)、≥纤维化分期2期(S2)及肝组织学明显异常(≥G2和/或≥S2)者分别为43例(15.75%)、30例(10.99%)及55例(20.15%)。17.95%患者存在肝脂肪变,98.17%肝组织乙型肝炎表面抗原(HBsAg)染色阳性,而肝组织乙型肝炎核心抗原(HBcAg)染色阳性仅为79.49%。不同性别组肝组织病理差异无统计学意义。肝组织HBsAg不同染色程度间炎症分级(G)和纤维化分期(S)的总体差异无统计学意义,而肝组织HBcAg不同染色程度间G和S的总体差异有统计学意义。单因素及多因素分析显示,影响肝组织病理严重程度的独立危险因素主要为肝组织HBcAg染色强度(负相关)、HBeAg水平(负相关)、年龄(正相关)等;但≤30岁组与>30岁组、≤40岁组与>40岁组的肝组织G和S差异均无统计学意义。虽然诊断模型肝脏炎症和纤维化5项指数(LIF-5)的判断价值优于天冬氨酸转氨酶和血小板计数比率指数(APRI)及肝纤维化4因子指数(FIB-4),但三者判断肝组病理严重程度的曲线下面积(AUC)均不高(<0.8),只有LIF-5判断≥G2、≥G2和/或≥S2的特异度在80%以上。结论约20%的IT期慢性HBV感染者存在明显肝组织炎症活动或纤维化进展,肝组织HBcAg染色强度和HBeAg水平与其严重程度负相关,诊断模型或多数临床指标对该类人群的评估价值均不高。

Objective To analyze the liver pathology,clinical characteristics and influence factors in patients with chronic hepatitis B virus(HBV)infection in immune tolerant phase(IT).Methods The clinical data of 273 patients in IT phase who underwent liver biopsy from January 2015 to December 2019 were included in this study.The correlation between liver pathological changes and clinical features was analyzed.Results There were 43 cases(15.75%)with liver histologic activity≥G2,30 cases(10.99%)with liver fibrosis≥S2,and 55 cases(20.15%)with liver pathology≥G2 and/or≥S2.A total of 17.95%patients had liver steatosis.The majority(98.17%)of tissue samples were positive for HBsAg staining,while only 79.49%were positive for HBcAg.The characteristics of liver pathology were comparable in men from women patients.The differences of G and S were not statistically significant according to different HBsAg positivity,while those were statistically significant according to different HBcAg positivity.By univariate and multivariate analysis,the independent risk factors of pathological severity were HBcAg intensity,HBeAg level,and age.However,the differences of liver histologic activity and fibrosis were not statistically significant between those younger than 30 years old group from those older than 30 years old,neither between those younger or older than 40.Although the diagnostic value of liver inflammation and fibrosis 5(LIF-5)was better than that of aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis 4 score(FIB-4),three diagnostic models for predicting the pathological severity were not strong enough(all area under the curves<0.8).Only the specificity of LIF-5 for predicting≥G2,≥G2 and/or≥S2 was over 80%.Conclusions Approximately 20%patients with chronic HBV infection in IT phase have progressive liver inflammation or fibrosis.The intensity of liver HBcAg and HBeAg level are negatively correlated with the severity of disease.The diagnostic models or most clinical indicators have low predictive effect for chronic HBV infections in IT phase.